Abstract
Pure Gō models (where every native interaction equally stabilizes the folded state) have widely proved their convenience in the computational investigation of protein folding. However, a chemistry-based description of the real interactions also provides a desirable tune in the analysis of the folding process, and thus some hybrid Gō potentials that combine both aspects have been proposed. Among all the noncovalent interactions that contribute to protein folding, hydrogen bonds are the only ones with a partial covalent character. This feature makes them directional and, thus, more difficult to model as part of the coarse-grained descriptions that are typically employed in Gō models. Thanks to a simplified but rigorous representation of backbone hydrogen bonds that we have recently proposed, we present in this article a combined potential (Gō + backbone hydrogen bond) to study the thermodynamics of protein folding in the frame of very simple simulation models. We show that the explicit inclusion of hydrogen bonds leads to a systematic improvement in the description of protein folding. We discuss a representative set of examples (from two-state folders to downhill proteins, with different types of native structures) that reveal a relevant agreement with experimental data.